In 1971, Kjell Kleppe, working in Nobel laureate H. Gobind Khorana's lab at MIT, published in the Journal of Molecular Biology the precise conceptual description of the mechanism that decades later would be called PCR: using two primers flanking a specific DNA region and replicating it enzymatically with a polymerase. The logical design of the technique was complete. Limitations of the era — manual primer synthesis taking months, and a polymerase destroyed by heat — prevented automation. This paper was formally recognized as "prior art" in PCR patent battles. Mullis cited this work as a direct conceptual antecedent.